Is DBNDD2 p.Gly52Ala (c.155G>C) pathogenic?

DBNDD2 p.Gly52Ala (c.155G>C) is classified Uncertain significance in DBNDD2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-24). AlphaMissense: likely benign (0.1151); Ultra-rare (popmax 0.0181%, afr).

How common is DBNDD2 p.Gly52Ala (c.155G>C) in the general population?

DBNDD2 p.Gly52Ala (c.155G>C) is ultra-rare (popmax 0.0181%, afr) (gnomAD).

What do computational predictors say about DBNDD2 p.Gly52Ala (c.155G>C)?

AlphaMissense predicts likely benign (score 0.1151) — an in-silico prediction, not a clinical call.

DBNDD2 p.Gly52Ala

c.155G>C · VCV3499781

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1151 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0181%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1151	likely benign
REVEL	0.066	moderately benign-leaning
SaProt	LLR -5.11	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.8	GERP 0.82, phastCons 1
Overall
CADD	19.17	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0181% African / African-American · 12/66,456 alleles

Filtering AF 0.0104% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00807%

Overall 0.000907% 13/1,433,454 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0181%	5,538
Remaining individualsnot grpmax-eligible	0.00183%	54,624

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: DBNDD2
Protein: p.Gly52Ala
Coding: c.155G>C
MANE Select: NM_001048225 · reported on NM_018478
Type: single nucleotide variant
Location: chr20:45406606 (GRCh38)
Gene constraint: LOEUF 1.061 · pLI 0.02 (gnomAD)
Structure: AlphaFold pLDDT 60.09
Residue 52: the 'disordered' region

Full DBNDD2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DBNDD2 c.78G>T Uncertain significance ★ same type
DBNDD2 c.95C>A Uncertain significance ★ same type
DBNDD2 c.-146C>T Uncertain significance ★ same type
DBNDD2 c.-15C>A Uncertain significance ★ ⚠ same type
DBNDD2 c.-29G>T Uncertain significance ★ ⚠ same type
DBNDD2 c.-32C>T Uncertain significance ★ ⚠ same type
DBNDD2 c.-5C>A Uncertain significance ★ ⚠ same type
DBNDD2 c.-5C>T Uncertain significance ★ ⚠ same type

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/dbndd2-p-gly52ala (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown